Overall Objectives: The Pilot Project Program (PPP) is one of the most important components of the Center for Environmental Genetics (CEG). The primary objective of the PPP is to provide seed support for new initiatives in basic, translational, and clinical research that will shed new light on the interaction between genes and the environment in which they operate (see Section 1-Strategic Vision). The goal ofthe program is to allow investigators, either established or new to the field, to obtain significant preliminary data that can become the basis of a new grant proposal, R21/R01-type or K-series career development grant (or their equivalent) and associated publications. The program is also viewed by CEG, and judged by its Internal (lAB) and External Advisory Board (EAB), as an important vehicle to help junior investigators in their career development, recruit new investigators into the field of environmental health sciences (EHS) research, promote facility core usage, build trans-disciplinary teams for translation to population-based/clinical studies and promote community outreach and engagement activities. In essence, the PPP serves to integrate all other Center components through its award mechanisms, each help realizing the goals of the other CEG cores (see Fig. 1) CEG The PPP has been enormously successful in the past and during the last funding cycle [see subsections F, G & Table 1 below, and Tables D2, E1 and E2], in part due to its emphasis in supporting innovative, translational research that promotes career development and team science. Success of the PPP will continue to be measured by the following metrics: a) recruitment of new investigators at all levels to this area of research, b) subsequent attainment of independence among funded junior investigators, c) extramural funding generated from research supported by the PPP, d) new partnerships and research resources initiated with PPP support e) resulting publications with high impact in the field. Special attention is given to whether the funded projects uphold the collaborative and integrative nature of the CEG, highlight creativity in utilizing state-of-the-art technologies offered by the facilities and services cores, concentrate on the Center theme of gene-environment interaction through epigenetics in four focus areas (endocrine disruption and cancer, immune and allergic disease, cardiovascular and lipid disorder, neurology and behavior research), and have significant potentials in translation and community outreach. An important element of the PPP is to support synergistic, innovative, high-risk/high-reward research with a multidisciplinary foundation. The funding mechanisms for FY21-25 will be closely aligned to the mission of the CEG (see Section 1-Strategic Vision) and the two-track training model of the Career Development Core (CDC) (see Section 4-Career Development Core). Specifically, the PPP will use five award mechanisms (see Fig. 1): 1) Mentee-mentor Partnership Awards, 2) New-to-EHS Investigator -Awards,_3)-lnnovator_Awar.ds-for_established.investigators-to-pursue-a-new-direction-or_acquire/utilize-a.new_ technology, 4) Affinity Group Awards that aim at building functional multidisciplinary group research, and 5) Community Engagement in Research Awards. The five mechanism types assist the CEG in maintaining a diverse portfolio of research projects. The PPP will seek to fund projects that pioneer leading-edge EHS research directions and prepare future leaders in the forefront of research in gene-environment interactions. Given the availability ofthe Human Genome and the explosion of data from functional genomics, epigenetics, proteomics, metabolomics, and advances in exposure assessment, the PPP is especially interested in funding studies on human health or disease prevention using advanced technologies or transforming concepts. All PPP recipients will be fully supported by four state-of-the-art, highly integrated facilities and services cores: the Integrative Technologies Support Core (ITSC), the Bioinformatics Core, the Integrative Health Sciences Facility Core (IHSFC), and the Community Outreach and Engagement Core (COEC). Based on the Directors' vision to aggressively build EHS research capacity and bridge pipeline effort, the PPP is open to all faculty in the three participating institutions: the University of Cincinnati (UC), the Cincinnati Children's Hospital Medical Center (CCHMC) and the Cincinnati Veteran Affairs Hospital Medical Center (CVAMC). This policy has received strong endorsement from the lAB and EAB.